Prevention of diabetes in rats by bone marrow transplantation.
Hyperglycemia, hypoinsulinemia and ketonemia often develop abruptly in previously normal young "BB" rats. The syndrome mimics human juvenile diabetes closely and is, thus, appropriate for assessing pancreatic transplantation. Transplantation of islet cells from closely histocompatible Wistar Furth (WF) donor resulted in permanent normoglycemia when immunosuppression with ALS was given. However, when islet cells from nondiabetic "BB" donors were transplanted to nonimmunosuppressed diabetic "BB" recipients, only transient normoglycemia followed. Transplantation of WF islets cells also failed in diabetic "BB" rats which were tolerant of WF antigens, again suggesting destruction of transplanted islet cells by the original disease process-possibly autoimmunity. Evidence for autoimmunity was strengthened by the finding that newly diabetic "BB" rats could be rendered normoglycemic by immunosuppression. Since genetic susceptibility to spontaneous autoimmune diabetes is unique to some members of the "BB" stock, an attempt was made to alter their vulnerability by modifying their cellular immune system. Accordingly, 50 million bone marrow cells from WF donors were inoculated into half the newborn members of "BB" litters, leaving the littermates as unmodified controls. Most bone marrow recipients were protected, only four of 37 (10.8%) ever becoming diabetic, while the incidence of diabetes in noninoculated littermates was 22 of 39 (56.4%). The ultimate goal in human diabetes, which also seems very likely to be an autoimmune disease, may not be replacement of destroyed islet cells but identification of potentially susceptible children and prevention of islet destruction by immunologic manipulation.
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D016026:Bone Marrow Transplantation; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D004195:Disease Models, Animal; D007165:Immunosuppression Therapy; D016381:Islets of Langerhans Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D014184:Transplantation, Homologous
D001323:Autoantibodies